Top panels show images of cutaneous melanomas emphasizing the ABCD features
of Asymmetry, Border irregularity, Color variegation, and Diameter greater
than 6 mm. Scale bars represent approximately 5 mm. Bottom panels show the
back of a male patient with numerous moles, demonstrating evolution of 1 mole
into melanoma over an 11-month period. Note the increased diameter and darkening
of the lesion in the right panel compared with the left panel.

Context The incidence of cutaneous melanoma has increased over the past several
decades, making its early diagnosis a continuing public health priority. The
ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) acronym
for the appraisal of cutaneous pigmented lesions was devised in 1985 and has
been widely adopted but requires reexamination in light of recent data regarding
the existence of small-diameter (≤6 mm) melanomas.

Evidence Acquisition Cochrane Library and PubMed searches for the period 1980-2004 were conducted
using search terms ABCD and melanoma and small-diameter melanoma. Bibliographies of retrieved articles were
also used to identify additional relevant information.

Evidence Synthesis Available data do not support the utility of lowering the diameter criterion
of ABCD from the current greater than 6 mm guideline. However, the data support
expansion to ABCDE to emphasize the significance of evolving pigmented lesions
in the natural history of melanoma. Physicians and patients with nevi should
be attentive to changes (evolving) of size, shape, symptoms (itching, tenderness),
surface (especially bleeding), and shades of color.

Conclusions The ABCD criteria for the gross inspection of pigmented skin lesions
and early diagnosis of cutaneous melanoma should be expanded to ABCDE (to
include “evolving”). No change to the existing diameter criterion
is required at this time.

The ABCD acronym for melanoma screening was devised in 19851 to provide the lay public and primary health care
professionals with a useful and memorable mnemonic to aid in the early recognition
of potentially curable cutaneous malignant melanoma. Quiz Ref IDThe
now well-known parameters of Asymmetry, Border irregularity, Color variegation,
and Diameter greater than 6 mm are used globally in medical education and
in the lay press to provide simple parameters for appraisal of pigmented cutaneous
lesions that may need to be further examined by a specialist. Specialist
evaluation may result in further workup of pigmented lesions via dermoscopy,
biopsy, or both.2

Over the course of their 19-year history, the ABCD criteria have been
widely described,3- 5 disseminated,6- 9 verified,3,4,10 and debated.11- 13 We review key literature
regarding the applications and utility of ABCD, revisit the D criterion in
light of recent data regarding small-diameter melanomas, and consider expansion
of the acronym to ABCDE, which includes a criterion for evolving (ie, lesions
that have changed over time).

EVIDENCE ACQUISITION

Cochrane Library and PubMed searches for the period 1980-2004 were conducted
using search terms ABCD and melanoma and small-diameter melanoma. The search was expanded using the bibliographies
of the initially retrieved articles. Articles pertaining to the ABCDs of dermoscopy,
a subject distinct from our own, were excluded. No systematic reviews, epidemiologic
case-control, or cohort studies were identified. In addition, there were no
controlled trials studying small melanomas (≤6 mm). Selected articles were
English-language, retrospective, clinicopathologic reports and case series
describing and quantifying small-diameter (≤6 mm) melanomas in adult patients.
Reports studying a minimum of 30 patients were considered, resulting in the
exclusion of 1 article. All identifiable articles, letters, and conference
proceedings addressing and critiquing the ABCD criteria for naked-eye examination
of pigmented skin lesions were reviewed.

EVIDENCE SYNTHESIS

Genesis, Validation, and Critique of the ABCDs

In 1985,1 members of our group devised
the ABCD acronym in response to an increasing melanoma incidence with little
to no public awareness. Indeed, melanoma incidence increased steadily in the
United States throughout the 20th century, most recently increasing from 7.5
per 100 000 in 1973 to 22.6 per 100 000 in 2001 among white populations
(the group at highest risk for melanoma).14 Despite
reports of cohort-specific improvements, overall melanoma incidence and mortality
continue to increase in the United States and elsewhere,15 making
the early recognition of melanoma a continuing public health priority.

The ABCD criteria were intended as a simple tool that could be implemented
in daily life, a mnemonic “as easy as ABC,” to alert both the
layperson and primary care physician to the clinical features of melanoma.
Based on our experience evaluating patients in the Melanoma Cooperative Group
at New York University School of Medicine, we found that asymmetry, border
irregularity, and color variegation were consistently associated with lesion
diameter greater than 6 mm. These observations led to the creation of the
current A, B, C, and D criteria. This acronym was first described in 19851; in 1993, the research basis for ABCD was presented
more thoroughly.16

It should be emphasized that ulcerated lesions were excluded in the
initial analysis because we sought to elucidate features of early melanoma.
Pigmented skin lesions that were ulcerated without a history of antecedent
trauma would have been already highly suspicious for advanced melanoma and
would have required biopsy regardless of other features, justifying their
exclusion from analysis. The ABCDs were thus intended to help describe a subset
of melanomas, namely early, thin tumors16,17 that
might otherwise be confused with benign pigmented lesions. Also, it should
be emphasized that the criteria were developed to assist nondermatologists
in differentiating common moles from cancer and were not meant to provide
a comprehensive list of all melanoma characteristics.

A few investigators have critiqued the original ABCD criteria in principle
and in practice.13,18- 20 Grob
pointed out that atypical nevi and seborrheic keratoses can share many of
the ABCD properties of melanomas.18 Nevertheless,
the ABCD criteria have been verified in 3 studies documenting their diagnostic
accuracy in clinical practice.3,4,10 As
shown in Table 1, the sensitivity and
specificity of these criteria vary when used singly or in combination, and
sensitivity declines as specificity increases. In addition, Barnhill et al
investigated interobserver variability and reported moderate but significant
agreement in most clinical features, including irregular borders and multiple
colors, among 4 physician evaluators (P<.001).21 The combination of reliable sensitivity and specificity
in addition to adequate interobserver concordance in the application of the
ABCD criteria supports the ongoing utility of this screening instrument in
clinical medicine. It should be emphasized that not all melanomas have all
4 ABCD features. It is the combination of features (eg, ABC, A+C, and the
like) that render cutaneous lesions most suspicious for early melanoma.

Revising the D Criterion: Increasing Evidence of Small Melanomas

While the A, B, and C criteria of 1985 have been widely accepted, a
growing body of literature documenting the existence of small-diameter melanomas,
defined as those 6 mm or less in diameter, has prompted us to reevaluate whether
the D criterion needs to be revised. We identified 6 retrospective reports
quantifying the prevalence of small-diameter cutaneous melanomas in cohorts
of at least 30 patients, including one by our own group.12,22- 26 Currently,
it is unclear what proportion of all melanomas are less than 6 mm in diameter,
and more importantly, what proportion of pigmented lesions 6 mm or less in
diameter are melanomas. Various authors report that small melanomas include
less than 1%27 to 38%24 of
all invasive melanomas.

Quiz Ref IDMost small-diameter melanoma studies are limited by
the fact that they are retrospective reviews of pathology specimens and do
not always consider the key issue of ex vivo tissue shrinkage in their analysis.
A notable exception is the 1999 article by Bono et al of 270 consecutive melanoma
cases,23 which measured melanoma diameters
on relaxed skin, prior to excision. Among all small-diameter melanoma studies
we reviewed, the methodology used by Bono et al most closely approximates
lesion measurement techniques used in clinical practice. In their series,
the authors found that 33 (14%) of 231 invasive melanomas were small-diameter
lesions.

Published data regarding melanoma specimen shrinkage have important
implications for the analysis of small melanoma data generated from histopathologic
specimens. Silverman et al28 performed the
largest available study of tissue shrinkage and found a mean, age-related
shrinkage of 20% comparing in vivo with postfixation measurements for 407
cutaneous melanomas. Using an algorithm based on these results, we determined
that lesion diameters reported in specimen-based studies as 4.8 mm or greater
postexcision may well have measured 6 mm or more in-vivo, before surgical
removal.

Based on available data, we reanalyzed 4 studies12,22,25,26 from
the literature on small-diameter melanomas using the formula of Silverman
et al28 to estimate the actual size of pigmented
lesions on patients’ skins. After adjusting for tissue shrinkage among
specimens from our Australian cohort,26 we
found that 10% of invasive melanomas were small-diameter tumors, in contrast
to the 31% previously reported. The results of the other 3 studies,12,22,25 which included lesions
mostly less than 5 mm in diameter, were little changed in our analysis. Data
from these studies suggested that small-diameter melanomas represented less
than 5% of all invasive melanomas. Since the literature on small-diameter
melanomas does not present data on the diameter of benign pigmented skin lesions
for comparison with malignant lesions, we do not know what proportion of all
small-diameter (ie, ≤6 mm) lesions are melanomas, an important consideration
if the D criterion is to be revised.

The outcomes of invasive small-diameter melanomas have not been well-established,
as existing reports focus on only short-term patient follow-up and presented
very limited long-term mortality data. Such outcomes may be best understood
in a framework that considers lesion thickness in addition to lesion diameter.
Tumor thickness, a measurement of tumor invasion into the dermis, is a powerful
prognostic factor and a key component for the staging of localized melanoma.29 In published data from other groups, small-diameter
melanoma tumor thicknesses ranged from 0.11 to 1.5 mm, with a median thickness
of approximately 0.7 mm.12,22,23,25,26 Studies
of melanoma outcome would predict a favorable prognosis for the majority of
such relatively thin tumors.29

In contrast to the short-term follow-up described above, we obtained
new follow-up data, ranging from 10 to 14 years, from the Australian cohort
on which we previously reported.26 Our focus
was to extract information regarding the specific question of mortality attributed
to small-diameter melanomas that could have been diagnosed based on the ABCD
criteria. We included patients with nonulcerated lesions measuring 6 mm or
less in diameter after adjustment for tissue shrinkage. Based on these inclusion
criteria, 2 patients died from nonulcerated, small-diameter (5.8 mm and 5.9
mm) melanomas. In contrast to the published reports we reviewed, both of our
patients had locally advanced, thick tumors, 2.1 mm and 3.8 mm in thickness,
respectively, with mitotic indexes of 18 and 5 mitoses/mm2. A mitotic
index greater than 5 mitoses/mm2 has been correlated with poor
prognosis, independent of tumor thickness in some studies.30,31 The
survival times of these patients were 52 and 14 months, respectively. No other
published studies reported patient deaths, although Kamino et al reported
1 recurrence and 1 metastasis after median follow-up of 16 months.25 Despite the lack of clarity regarding the proportion
and clinical course of small-diameter melanomas relative to all melanomas,
it appears that invasive melanomas 6 mm or less in diameter are uncommon and
such lesions infrequently cause metastatic disease since they are generally
removed at early stages of tumor progression.

Quiz Ref IDRevision of the D criterion depends less on the proportion
of small-diameter melanomas among all melanomas than on the frequency of small
melanomas (≤6 mm in diameter) among the universe of all pigmented cutaneous
lesions of similar diameters. This frequency would be difficult to calculate
as the vast majority of pigmented lesions 6 mm or less are obviously benign
and thus are not biopsied. Overall, it has been estimated that among pigmented
cutaneous lesions there are 90 000 benign nevi to every 1 melanoma.32 Based on the above considerations, we do not believe
that lowering the diameter criterion of the ABCD framework will increase sensitivity
of melanoma diagnosis without seriously compromising specificity and generating
millions of unnecessary skin biopsies. Costs, scarring from surgical procedures,
and patient anxiety must be considered in the estimation of public health
implications associated with lowering of the D criterion. The ABCDs
have the greatest diagnostic accuracy when used in combination, a concept
that should be kept in mind when evaluating pigmented lesions 6 mm or less
in diameter. When such small lesions have only 1 of the other ABC criteria,
follow-up observation of its evolution, if present, can lead to the eventual,
early diagnosis of cutaneous melanoma.

The Case for an E Criterion

The ABCD acronym was originally designed to provide the lay public and
physicians with easily memorable criteria to recognize the extant physical
characteristics of early melanomas. Since their description nearly 20 years
ago, evidence has accumulated that the addition of “E” for “Evolving”
will substantially improve and enhance the ability of physicians and laypersons
to recognize melanomas at earlier stages. “E” for Evolving recognizes
the dynamic nature of this skin malignancy. This is especially important for
the diagnosis of nodular melanomas, which frequently present at more advanced
stages (ie, thicker tumors), thus contributing greatly to melanoma mortality
rates.19,33,34

Quiz Ref IDNodular melanomas frequently lack asymmetry, border
irregularity, color variegation, and diameter greater than 6 mm.20,35 However,
in one series of 125 patients, lesion change (ie, evolution) was noted in
78% of nodular melanomas.20 Among the 92 patients
with the more common superficial spreading melanoma, 71% noted evolution of
their lesion.20 These data are consistent with
previous data from our group in which 615 (88%) of 696 patients noted evolution
in their melanoma prior to its removal.33

We support expansion of the ABCD criteria to include an E for evolving
(ie, lesion change over time) (Figure). Quiz Ref IDWe define “evolving lesions” as those noted to have changed
with respect to size, shape, symptoms (eg, itching, tenderness), surface (eg,
bleeding), or shades of color. Others have proposed various “E’s”
to be added to ABCD. We prefer the term “evolving” to “enlargement”4 because enlargement focuses on the size of a lesion
alone and excludes consideration of color changes, which are part of the evolution
of many melanomas. E for “elevation”36 would
be misleading because significant elevation is not apparent in most early
melanomas and is thus not a warning of early disease.5,26 “Evolving”
is a simpler term than “evolutionary change”13,37 and
could be more readily incorporated into public educational materials. The
term “evolving” subsumes the concepts of change, enlargement,
and elevation.

The importance of lesion evolution as a cardinal feature of cutaneous
melanoma, and a frequent cause of excision among lesions ultimately diagnosed
as melanoma, is well supported.4,25,30,32,38,39 Although
patient report has been criticized for its subjectivity in comparison with
more objective assessments of asymmetry, border, and color,17 a
2001 review by Grichnik of “difficult early melanomas” supports
the importance of soliciting patients’ history of lesion changes in
differentiating melanoma from atypical nevi.32 A
study by Cassileth et al of presenting symptoms in malignant melanoma found
that changes in “size, elevation and color” were the most frequent
cluster of symptoms reported by patients as catalysts precipitating medical
evaluation.38 Other symptoms noted to be significant
were bleeding, itching, tenderness, elevation, and ulceration.38

Three studies lend additional support to the importance of lesion evolution
in the diagnosis of cutaneous melanoma. Based on their calculation of the
sensitivities and specificities of each of 5 ABCDE criteria (using E for horizontal
enlargement, which is a feature of an evolving lesion), Thomas et al4 concluded that enlargement is the most specific criterion
among the ABCD(E)s (Table 1). Lucas
et al, in a study of dermoscopic features of 169 pigmented lesions, found
that lesions noted by dermatologists to be both nonuniform (ie, sharing some
of the ABC criteria) and changed had at least a 4 times greater chance of
being melanoma than lesions that did not meet these characteristics.40 The study by Healsmith et al of the sensitivity of
the ABCD(E) criteria in diagnosing 65 melanomas revealed that all 5 lesions
missed by the ABCDEs (with E for elevation) had been noted by the patient
to have evolved (ie, changed in size over time).3

The concept of lesion evolution has a prominent place in the Glasgow
7-point checklist, which highlights changes in size, shape, and color as major
signs of melanoma. As demonstrated in Table 2, the addition of E (for evolving) adds these major criteria to
the ABCDs. These criteria are based in part on the observation that 89% to
95% of 100 consecutively accrued melanomas demonstrated changes in these features,
and 100% showed change in at least 1 feature. Minor criteria in the checklist
include sensory change, diameter of 7 mm or greater, and the presence of inflammation,
crusting, or bleeding, as these were observed less frequently.41 Perhaps
due to its greater complexity, however, the Glasgow checklist has been less
widely adopted than the ABCD criteria.

Expansion to ABCDE will broaden the education of physicians and the
lay public in the clinically significant historical features of pigmented
cutaneous lesions, especially the evolving nature of early melanomas. Evidence
suggests this may improve the early diagnosis of melanoma. In 2001, Harris
et al published an Internet-based study of skin cancer education.42 This included modules on the recognition of melanoma
using an algorithm that combines the ABCD criteria with the importance of
a changing lesion, included in the Glasgow 7-point checklist. The study population
consisted of 354 physicians, 346 (92%) of whom were nondermatologists. The
authors reported that a statistically significant increase in the proper management
of pigmented lesions was observed. Specificity in the diagnosis of pigmented
lesions increased from 69% to 89% (P<.001), with
a small decrease in sensitivity, 95% to 91% (P<.001).
The authors’ comment that a single case of a small melanoma that developed
a change in color and was not biopsied by many participants accounted for
the decrease in sensitivity. Describing this finding they state, “This
information allows us to improve our program by reemphasizing the need to
consider ‘change’ as well as the static characteristics of a lesion.”

Data from a population-based study in Connecticut demonstrated that
increased patient awareness of melanoma signs and symptoms was significantly
associated with decreased time to seek medical attention and decreased tumor
thickness.43 The results of a public education
program in western Scotland demonstrated a decrease in the diagnosis of melanomas
greater than 3.5 mm thick (34% to 15%) with a simultaneous increase in the
diagnosis of thinner melanomas, defined as less than 1.5 mm thick (38% to
62%). It was speculated that this shift in diagnoses to early stage disease
could result in lower health care costs, as the management of thinner lesions
is less costly than that of thicker lesions.44 The
importance of public education in the clinically significant features of pigmented
cutaneous lesions is also underscored by data from a 1992 population-based
survey of incident cases of melanoma in Massachusetts that reported only 26%
of all melanomas are identified by medical service clinicians; the remainder
were diagnosed by patients themselves (53%) or by their family members (17%).45

CONCLUSIONS

The ABCD criteria for the assessment of pigmented cutaneous lesions
has been a useful screening tool in the diagnosis of melanoma, supported by
evidence of reasonable sensitivity and specificity for melanoma diagnosis.
While current literature reports the existence of invasive “small-diameter
melanomas,” these lesions appear to be uncommon. We support preservation
of the original greater than 6 mm D criterion.

In contrast, our review of the literature has led us to endorse the
inclusion of “E” for “evolving,” emphasizing change
over time as an important additional criterion in differentiating melanoma
from benign pigmented lesions. Although not all changes in moles denote the
presence of melanoma, lesions that have changed warrant further examination
and possible biopsy. Future educational programs and literature about melanoma
should emphasize the importance of a history of change (ie, evolving) in the
assessment of pigmented cutaneous lesions. Organizations including the American
Cancer Society and Skin Cancer Foundation have promoted lesion change in their
educational materials; however, this feature has been described in paragraphs
of text, without adequate emphasis.6- 9 By
adding “E” for “evolving” to the well-known ABCDs,
we are stressing the importance of “E” in a more simplified message
than is currently available. We believe that ABCDE is a simple, succinct,
and memorable tool to educate the public, and the nondermatology and dermatology
medical community about the key features of melanoma, especially lesion change.

We urge broad physician and public education in the use of the ABCDE
criteria, as evidence suggests that even one-time instruction in the proper
management of pigmented cutaneous lesions can result in immediate improvement
in the capacity of clinicians and laypersons to identify cutaneous melanomas.42,46 We believe that such education will
enhance the timely diagnosis of cutaneous melanoma, resulting in the surgical
removal of such cancers when they are still curable.

Corresponding Author: David Polsky, MD,
PhD, Ronald O. Perelman Department of Dermatology, New York University School
of Medicine, 550 First Ave (H-100), New York, NY 10016 (David.Polsky@med.nyu.edu).

Funding/Support: Dr Polsky is supported in
part by NIH grant K08 AR02129 and by the use of facilities at the Manhattan
Veterans Affairs Medical Center, New York, NY.

Role of the Sponsor: The funding organizations
did not participate in the design and conduct of the study; in the collection,
analysis, and interpretation of the data; or in the preparation, review, or
approval of the manuscript.

Acknowledgment: We gratefully acknowledge Richard
A. Scolyer, MD, for his assistance with histopathologic remeasurement of melanoma
specimens from our Australian patient cohort, and Caroline Chang for her assistance
in preparation of the Figure and Table 1.